Rat C6 glioma cells contain a beta-adrenergic receptor, stimulation of which leads to an induction of a specific foirm of cyclic nucleotide phosphodiesterase (PDE). The induction of PDE is shown to require a rise in cyclic AMP, activation of cAMP-dependent protein kinase, translocation of the catalytic subunit of the kinase to the nucleus, phosphorylation of non-histone chromosomal proteins, and RNA polymerase II. Inhibition of one of these steps by drugs such as colchicine, cordycepin or alpha-amanitin prevents PDE induction. Direct measurement of mRNA levels can be made using CDNA probes. Treatment of bovine adrenal chromaffin cells with 8-Br-cyclic AMP results in an increase of both proenkephalin (PE) and tyrosine hydroxylase mRNA in these cells, which is time-- and dose-dependent and not replicated by 8 - Br - cyclic GMP. There is a comparable change in the content of enkephalin-kike peptides. Use of cDNA probes for PE and for proopiomelanocortin (POMC) has shown a differential distribution of the mRNAs in the CNS as well as differential regulation by such chronic drug treatments as haloperidol, reserpine, fenfluramine or 5,7-dihydroxytryptamine. Certain drugs alter peptide content by increasing biosynthesis of the mRNA whereas others act at the level of utilization.